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Cellular-level characterization of B cells infiltrating pulmonary MALT lymphoma tissues

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Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma mainly consists of three types of tumor B cells, small (centrocyte-like), scattered large transformed, and intraepithelial. However, it is difficult to differentiate tumor B cells from reactive B cells at the cellular level. We examined five cases of API2-MALT1 fusion-positive MALT lymphoma of the lung. A single paraffin section for each case was subjected to sequential retrieval of whole-slide imaging (WSI) data of hematoxylin and eosin (HE) staining, immunofluorescence staining for CD79a, and fluorescence in situ hybridization (FISH) for the MALT1 split. We counted the number of MALT1 split-positive or MALT1 split-negative cells among CD79a-positive cells. The MALT1 split was detected in 59, 46, and 76 % of small, large, and intraepithelial B cells, respectively. A review of the HE-WSI data showed that cytomorphological distinction between the MALT1 split-positive and MALT1 split-negative B cells was virtually impossible. None of CD79a-negative lymphoid cells, epithelial cells, and microvascular endothelial cells was positive for MALT1 splits. As API2-MALT1 fusion is an early and critical event in the lymphomatogenesis, our findings are best interpreted as that a considerable number of B cells, either small, large, or intraepithelial, are reactive cells and that it is difficult to distinguish cytomorphologically between tumor B cells and reactive B cells. These findings suggest that the tumor architecture may be the central factor for making a correct histopathological diagnosis of MALT lymphoma. The sequential WSI of HE staining, immunofluorescence staining, and FISH as described here is a useful tool for pathological analysis at the cellular level.

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Authors and Affiliations

  1. Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Keiichiro Fujii, Ken-ichiro Ishibashi, Junki Kato, Jushin Kan, Kana Fujii, Yohei Ito, Hisashi Takino, Ayako Masaki, Takayuki Murase & Hiroshi Inagaki

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  1. Keiichiro Fujii
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  2. Ken-ichiro Ishibashi
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  3. Junki Kato
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  4. Jushin Kan
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  5. Kana Fujii
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  6. Yohei Ito
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  7. Hisashi Takino
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  8. Ayako Masaki
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  9. Takayuki Murase
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  10. Hiroshi Inagaki
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Correspondence to Hiroshi Inagaki.

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All research protocols were approved by the institutional review board of Nagoya City University (#113) and conformed to the provisions of the Declaration of Helsinki.

Funding

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (15K08351 to H. Inagaki).

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The authors declare that they have no conflict of interest.

Electronic supplementary material

Fig. S1

Detection of MALT1 splits in CD79a-negative lymphoid cells (A-C), epithelial cells (D and E), and microvascular endothelial cells (F and G). None of these cells shows MALT1 split. Asterisks indicate lymphoid cells negative for CD79a (B). White arrows indicate fused (unaltered) MALT1 signals (C, E, and G). Cilia of the epithelial cells are indicated by an orange arrow (D). HE stain (A, D, and F), immunostain for CD79a (B), and FISH for MALT1 split (C, E, and G). (PPT 3262 kb)

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Fujii, K., Ishibashi, Ki., Kato, J. et al. Cellular-level characterization of B cells infiltrating pulmonary MALT lymphoma tissues. Virchows Arch 469, 575–580 (2016). https://doi.org/10.1007/s00428-016-2012-z

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  • DOI: https://doi.org/10.1007/s00428-016-2012-z

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